An effective method of combating infectious diseases is the deployment of hand-held devices at the point-of-care (POC) for screening or self-monitoring applications. There is a need for very sensitive, low-cost and quantitative diagnostic devices. In this study, we present a low-cost, multiplexed fluorescence detection platform that has a high sensitivity and wide dynamic range. Our system features inexpensive 3×3 mm interference filter with a high stopband rejection, sharp transition edges, and greater than 90% transmission in the passband. In addition to the filters we improve signal-to-noise ratio by leveraging time for accuracy using a charge-integration-based readout. The fluorescence sensing platform provides a sensitivity to photon flux of ∼1×104 photons/mm2sec and has the potential for 2 to 3 orders of magnitude improvement in sensitivity over standard colorimetric detection that uses colored latex microspheres. We also detail the design, development, and characterization of our low-cost fluorescence detection platform and demonstrate 100% and 97.96% reduction in crosstalk probability and filter cost, respectively. This is achieved by reducing fi r dimensions and ensuring appropriate channel isolation in a 2×2 array configuration. Practical considerations with low-cost interference fi system design, analysis, and system performance are also discussed. The performance of our platform is compared to that of a standard laboratory array scanner. We also demonstrate the detection of antibodies to human papillomavirus (HPV16) E7 protein, as a potential biomarker for early cervical cancer detection in human plasma.